Decitabine Combined With Modified CAG Versus Standard 3+7 Regimen For Induction Of The Medically Fit Elderly Acute Myeloid Leukemia

Purpose:Acute myeloid leukemia(AML)is the most common acute leukemia in adults,with more than half of patients being>60 years old.The induction treatment for the medically fit elderly acute myeloid leukemia remains controversial.Studies have shown that decitabine combined with chemotherapy can achieve certain efficacy in elderly patients with AML.This prospective study compared the efficacy and safety of the decitabine combined with modified CAG(D-CAG)and standard 3+7 regimen in medically fit elderly patients with newly diagnosed AML.Patients and Methods:This study is a multicenter,open-label,randomized phase Ⅲ trial.Inclusion criteria:1)age 60 to 75 years old;and 2)in medically fit.Exclusion criteria:1)acute promyelocytic leukemia(M3);2)Uncontrolled infection including active tuberculosis;3)liver dysfunction(total bilirubin≥2 times the upper limit of normal[ULN]or alanine amino transferase(ALT)or aspartate aminotransferase(AST)≥2×ULN);4)renal dysfunction(creatinine≥2 × ULN or creatinine clearance<30mL/min);5)severe concomitant conditions not suitable for the trial,such as cardiovascular disease or psychiatric disorders.Screening fit elderly AML patients according to the inclusion and exclusion criteria.The patients were enrolled the clinical trial after signing the informed consent form.Patients were randomly assigned 1:1 to receive the D-CAG or 3+7 regimen.D-CAG regimen:Decitabine of 25mg/m2 for five consecutive days,followed by aclarubicin of 10mg/day for 4 days,cytarabine of 10 mg/m2 q12 h for 7 days,and G-CSF of 300ug from day 1-7 for priming until white blood count was>20G/L.Standard 3+7 regimen:idarubicin 8-10mg/m2(>70 years idarubicin 8 mg/m2)on days 1-3 and cytarabine 100mg/m2 on days 1-7.The primary endpoint was 1-year overall survival(OS).Results:Between March 2015 and May 2019,156 patients were enrolled in this study.The baseline and post-remission treatment characteristics of patients are balanced in two groups.CR rate were 56.4%and 59.0%after the first cycle(p=0.746),and 69.2%and 70.5%after two cycles(p=0.861)in the D-CAG and 3+7 groups,respectively.There was no also statistically difference of overall remission rate(ORR)after two cycles between two groups(80.7%vs 75.6%,P=0.438).Median follow-up was 29.5 months,one-year OS was significantly higher in the D-CAG group than 3+7 group(70.7%vs 56.6%,p=0.047),but 3-year OS were similar in two groups(31.1%vs 33.1%,p=0.642).The 90-day TRM was lower in the D-CAG than 3+7 groups(5.1%vs 15.4%,p=0.038).The 3-year cumulative incidence of relapse was higher in the D-CAG than 3+7 groups though had no significant difference(58.7%vs 33.4%,p=0.235).Multivariate analysis revealed that allo-HSCT and negative minimal residual disease in first complete remission were favourable factors for OS,EFS and reducing relapse.Conclusion:D-CAG regimen has lower TRM during induction treatment and improve early survival,but there is no benefit to long-term survival due to a higher tendency of relapse rate compared with 3+7 regimen for medically fit elderly AML patients.